Impaired bone status occurs in both women and men with advancing age. Research is focused on reversing the effects of aging on bone. The main goal of this project is to establish animal models which can be used to define age-deficits in bone activity at the cellular and molecular levels and to design and test the effectiveness of novel treatment procedures for osteoporosis. Local infusion of IGF-I into femurs of old rats stimulates expression of osteoblast genes and increases bone volume. This result suggests that growth factor therapy may be useful in osteoporosis. Minocycline treatment of old rats prevents bone loss in two ways: by stimulating bone formation and by reducing bone resorption. Reduced bone formation and increased bone resorption are common in osteoporosis. Minocycline therefore may be superior to other treatments that correct either bone resorption or bone formation but not both.